A carotenoid-enriched extract from pumpkin delays cell proliferation in a human chronic lymphocytic leukemia cell line through the modulation of autophagic flux

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in adult population.From an asymptomatic state, which can lay for years, CLL rapidly evolves becoming fatal.Apoptosis resistance and induction of a protective form of autophagy are possible explanations ofthe poor responsivity of CLL to conventional and innovative therapeutic drugs. Carotenoids,including ?- and ?-carotene, lycopene, and derivatives, such as retinoic acid, have been studied fortheir significant antiproliferative and differentiating activity in cancer. Here, we report that acarotenoid-enriched extract (CE) obtained from pumpkin by supercritical CO2 extraction showed ananti-proliferative effect on HG3 cell line derived from human B-CLL cells. CE induced a 40Þlay in cell proliferation compared to untreated cells, without signs of cytotoxicity. This delay wasassociated with p27Kip1 over-expression, AMPK activation and modulation of autophagy flux. InHG3 cells treated with CE, we detected a 30% autophagosome intracellular increase and changes inthe expression of canonical biochemical markers of autophagy (LC3-II, p62). These results suggestthe presence in the CE of a pool of bioactive carotenoids acting additively or synergistically inretarding cancer cell growth.